STEROID HORMONES, HIV-INFECTED CELLS AND HIV GENES

该项目旨在做两件事：第一，测试 假设类固醇激素效应的变化与 艾滋病毒的直接和间接细胞病变；第二，使用 作为顺式活性对照的糖皮质激素DNA反应元件 以定量确定它们的功能。 类固醇激素直接对淋巴细胞有深远的影响 也间接地通过影响许多多肽荷尔蒙 以及它们的受体。我们将研究类固醇的影响 HIV感染者外周血淋巴样细胞的研究 在几个受感染的细胞系上。这将需要研究 类固醇的细胞效应，类固醇受体的分析，以及 类固醇与几种药物相互作用的研究 多肽激素及其受体。有限的报道引发了 艾滋病毒是糖皮质激素诱导的可能性。我们会 彻底测试这种可能性。 几个HIV基因的确切功能尚不清楚，正如 特定基因产物与基因序列之间的定量关系 总体艾滋病毒复制和细胞病变。我们将把 顺式病毒中来自MMTV LTR的糖皮质激素反应元件 与艾滋病毒或特定艾滋病毒基因的关系，以提供 糖皮质激素可调节的HIV基因在转基因中的研究 细胞。我们的CEM细胞克隆系具有已知的病变 糖皮质激素反应系统，应该在 这些研究。

This project is designed to do two things: first, to test the hypothesis that changes in steroid hormone effects are involved in the direct and indirect cytopathicity of HIV; and second, to use a DNA response element for glucocorticoids as a cis-active control over HIV genes to determine their functions quantitatively. Steroid hormones have profound effects on lymphoid cells directly and also indirectly, through influences on many peptide hormones and their receptors. We will investigate the effects of steroids on peripheral blood lymphoid cells of HIV infected individuals and on several infected cell lines. This will require studies of cellular effects of steroids, analysis of steroid receptors, and examination of the interactive effects of steroids with several peptide hormones and their receptors. Limited reports raise the possibility that HIV is glucocorticoid-inducible. We will thoroughly test this possibility. The exact function of several HIV genes is unknown, as are the quantitative relationships between specific gene products and overall HIV replication and cytopathicity. We will place the glucocorticoid response element from the MMTV LTR in a cis relationship to HIV or specific HIV genes, to provide glucocorticoid-regulatable HIV genes for study in transfected cells. Our clonal lines of CEM cells with known lesions in the glucocorticoid response system, should be of particular value in these studies.